Diazabicyclooctane compounds

Abstract

The present invention relates to compounds according to Formula (II): or a stereoisomer, tautomer or pharmaceutically acceptable salt or ester thereof, wherein A, R 1 and R 2 are defined herein. Also described are pharmaceutically acceptable compositions of Formula (II) compounds as well as methods for utilizing the compounds of Formula (II) and the pharmaceutically acceptable compositions of Formula (II) compounds as antibacterial agents and β-lactamase inhibitors, useful in the treatment of infectious diseases.

The invention claimed is: 
     
       1. A compound of Formula (II) 
       
         
           
           
               
               
           
         
         wherein 
         R 1  is benzyl, H or SO 3 M; 
         M is H, or an inorganic or organic cation; 
         R 2  is H, (C 1 -C 8 )alkyl, —NHC(O)CH 2 -aryl, —NHC( O )CH 2 -heteroaryl, —NHC(O)CH(NH 2 )-aryl or —NHC(O)(CH 2 ) 3 CH(NH 2 )—CO 2 R 3 ; 
         A is a 5- to 6-membered heterocyclic ring containing at least one nitrogen atom and substituted with one or more groups selected from halogen, CN, (C 1 C 8 )alkyl, (C 1 -C 8 )haloalkyl, (C 2 -C 8 )alkenyl, (C 2 -C 8 )alkynyl, OR 3 , NR 3 R 3 , C(O)R 3 , [(C 1 -C 8 )alkylene]OR 3 , [(C 1 -C 8 )alkylene]OC(O)R 3 , [(C 1 -C 8 )alkylene]OC(O)NR 3 R 3 , [(C 1 -C 8 )alkylene]NR 3 R 3 , C(O)NR 3 R 3 , C(O)[(C 1 -C 8 )alkylene]NR 3 R 3 , CO 2 R 3 , C(S)NR 3 R 3 , SR 3 , S(O)R 3 , SO 2 R 3  and SO 2 NR 3 R 3 ; 
         R 3  is independently H, (C 1 -C 8 )alkyl, (C 1 -C 8 )haloalkyl, cycloalkyl, heterocyclyl, [(C 1 -C 8 )alkylene] heterocyclyl, aryl, [(C 1 -C 8 )alkylene] aryl or heteroaryl; and 
         wherein any alkyl, cycloalkyl, heterocyclyl, heteroaryl or aryl is optionally substituted with 1, 2, or 3 groups selected from OH, CN, SH, SO 2 NH 2,  halogen, NH 2 , NHCNH, C(O)NH 2 , C(O)N(CH 3 ) 2 , C(O)NH(aryl-COOH), C(NH)CH 3 , CH 2 (NH)SO 2 NH 2 , COOH, COOCH 3 , acetyl, (C 1 -C 8 )alkyl, S(C 1 -C 8 )alkyl, S(C 1 -C 8 )alkyl, (C 2 -C 8 )alkenyl, (C 2 -C 8 )alkynyl, (C 1 -C 8 )haloalkyl, (C 1 -C 8 )thioalkyl and heterocyclyl, 
         or a pharmaceutically acceptable salt or ester thereof. 
       
     
     
       2. The compound of  claim 1  wherein R 1  is SO 3 M. 
     
     
       3. The compound of  claim 1  wherein R 2  is (C 1 -C 8 )alkyl. 
     
     
       4. The compound of  claim 1  wherein A is a 5-membered heterocyclic ring containing one nitrogen atom. 
     
     
       5. The compound of  claim 1  wherein A is a 5-membered heterocyclic ring containing one nitrogen atom and one oxygen atom. 
     
     
       6. The compound of  claim 1  wherein A is a 5-membered heterocyclic ring containing one nitrogen atom and one sulfur atom. 
     
     
       7. The compound of  claim 1  wherein A is a 5-membered heterocyclic ring containing one nitrogen atom and substituted with (C 1 -C 8 )alkyl, COOH or SR 3 , wherein R 3  is heterocyclyl. 
     
     
       8. The compound of  claim 1  that is 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or ester thereof. 
       
     
     
       9. A pharmaceutical composition comprising a compound of Formula (II), according to  claim 1 , in combination with a pharmaceutically acceptable carrier, diluent or excipient. 
     
     
       10. A method for treating a bacterial infection in a mammal in need thereof comprising administrating to the mammal (i) a therapeutically effective amount of at least one compound according to  claim 1  or a stereoisomer, tautomer or pharmaceutically acceptable salt or ester thereof, or (ii) a pharmaceutical composition of  claim 9 .